Fandy Albert Gunawan Gosal, Trina Ekawati Tallei, Christina Leta Salaki, Diana Vanda Daturara Doda, Jumriani, Widya Hardiyanti, Jinwon Choi, Min Choi, Amama Rani, Firzan Nainu, Bonglee Kim
Abstract
Propolis is a bee-derived product rich in flavonoids and phenolics with reported antimicrobial, anti-inflammatory, and antioxidant activities, yet its coordinated effects on innate immunity and stress responses remain incompletely defined. The aim of this study was to determine how propolis modulates coupled immune–redox pathways and associated cell-fate signaling using an in vivo Drosophila melanogaster autoinflammatory model with heightened Imd/NF-κB reactivity due to impaired peptidoglycan degradation, following challenge with heat-killed Escherichia coli (HKE). Propolis (2.5%, 5%, and 10%) did not significantly affect developmental survival in the absence of HKE, supporting tolerability at the tested doses. Under HKE challenge, propolis improved survival in a dose-dependent manner, reduced ROS levels, and increased sod2 expression, consistent with strengthened antioxidant capacity. Immune output assessed by diptericin (dpt) was modulated in a dose-dependent, non-linear pattern, consistent with recalibration rather than uniform suppression of Imd signaling. HKE increased p53 expression, and propolis further elevated p53 without concomitant amplification of the intrinsic apoptosis marker debcl, suggesting stress-responsive engagement without escalation toward intrinsic apoptosis. In parallel, LC–HRMS profiling of the tested extract informed network pharmacology analyses, which suggested convergence of propolis constituents on pathways linked to inflammatory signaling, redox regulation, and survival-related stress responses, consistent with the in vivo phenotype. These findings nominate conserved immune–redox pathways as candidate mediators of propolis protection that warrant targeted functional validation.
* THESE STATEMENTS HAVE NOT BEEN EVALUATED BY THE FOOD AND DRUG ADMINISTRATION. THIS IS NOT INTENDED TO DIAGNOSE, TREAT CURE OR PREVENT ANY DISEASE.